Abstract
HLA-B27 represents a family of closely related antigens. Six alleles which differ in a limited number of nucleotide substitutions have been described (B*2701—B*2706). These changes are clustered in α1 and α2 domains. Polymerase chain reaction strategies were designed to amplify specific regions of class I exons 2 and 3. Amplified sequences were tested with eight sequence-specific oligonucleotides to distinguish all B27 subtypes. We also subtyped B27 in 50 healthy Spanish individuals using this procedure. The B*2705 subtype is over-represented in our population (96%). The remaining 4% carried the B*2702 allele. This finding is in agreement with the frequencies described by other techniques (cytotoxic T lymphocytes and isoeletric-focusing) for Caucasian populations. Class I oligotyping is a poorly developed field with significant potential applications. This procedure of genotyping B27 alleles is a reliable method which can be used in transplantation and B27-associated disease studies.
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Beatty, P. G., Layrisse, Z., Van Seventer, G. A., Fan, L., Magli, C., Ivanyi, P., Jenkin, J., and Hansen, J. A.: T-cell recognition of HLA class I molecules. In Bo Dupont (ed.): Immunobiology of HLA: pp. 359–362, Springer, New York, 1989
Benjamin, R. and Parham, P.: Guilt by association: HLA-B27 and ankylosing spondilitys. Immunol Today 11: 137–142, 1990
Benjamin, R. J., Madrigal, J. A., and Parham, P.: Peptide binding to empty HLA-B27 molecules of viable human cells. Nature 351: 74–77, 1991
Bjorkman, P. and Parham, P.: Structure, function, and diversity of HLA-class I Major Histocompatibility Complex molecules. Annu Rev Biochem 59: 253–258, 1990
Breuning, M. H., Lucas, C. J., Breur, B. S., Engelsma, M. Y., de Lange, G. G., Dekker, A. J., Biddison, W. E., and Ivanyi, P.: Subtypes of HLA-B27 detected by cytotoxic T lymphocytes and their role in self recognition. Hum Immunol 5: 259–268, 1982
Breur-Vriesendorp, B. S., Dekker, A. J., Breuning, M., and Ivanyi, P.: Subtypes of antigen HLA-B27 (B27W and B27K) defined by cytotoxic T lymphocytes. In M. Ziff and S. B. Cohen (eds.): Advances in Inflammation Research Vol 9. The Espondyloarthropaties, pp. 55–65, Raven Press, New York, 1985
Breur-Vriesendorp, B. S., De Waal, L. P., and Ivanyi, P.: Different linkage disequilibria of HLA-B27 subtypes and HLA-C locus alleles. Tissue Antigens 32: 74–77, 1988
Calvo, V., Rojo, S., López, D., Galocha, B., and López de Castro: Structure and diversity of HLA-B27 specific T cell epitopes. J Immunol 144: 4038–4045, 1990
Choo, S. Y., Antonelli, P., Nisperos, B., Nepom, G. T., and Hansen, J. A.: Six variants of HLA-B27 identified by isoelectric-focusing. Immunogenetics 23: 24–29, 1986
Choo, S. Y., John, T. S., Orr, H. T., and Hansen, J. A.: Molecular analysis of the variant alloantigen HLA-B27d (HLA-B*2703) identifies a unique single amino acid substitution. Hum Immunol 21: 209–219, 1988
Ezquerra, A., Bragado, R., Vega, M. A., Strominger, J. L., Woody, J. M., and López de Castro, J. A.: Primary structure of papainsolubilized human histocompatibility antigens HLA-B27. Biochem 24 : 1733–1744, 1985
Fleischhauer, K., Kernan, N. A., O'Reilly, R. J. B., and Yang, S. Y.: Bone marrow-allograft rejection by lymphocytes recognizing a single aminoacid defference in HLA-B44. N Engl J Med 323: 1818–1822, 1990
Hill, A. V. S., Allsopp, C. E. M., Kwiatkowski, D., Anstey, N. M., Greenwood, B. M., and McMichael, A. J.: HLA class I typing by PCR: HLA-B27 and an African B 27 subtype. Lancet 337: 640–642, 1991
López de Castro, J. A.: HLA-B27 and HLA-A2 subtypes: structure, evolution and function. Immunol Today 10: 239–246, 1989
Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C.: The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353: 321–325, 1991
Morel, C., Zwahlen, F., Jeannet, M., Mach, B., and Tiercy, J. M.: Complete analysis of HLA-DQB1 polymorphism and DR-DQ linkage disequilibrium by oligonucleotide typing. Hum Immunol 229: 64–67, 1990
Neefjes, J. J., Breur-Vriesendorp, B. S., Van Seventer, G. A., Ivanyi, P., and Ploegh, H. L.: An improved biochemical method for the analysis of polymorphism of HLA class I antigens. Definition of new HLA class-I subtypes. Hum Immunol 16: 169–181, 1986
Ness, D. B., and Grumet, F. C.: New polymorphism of HLA-B27 and other B-locus antigens detected by RFLP using a locus-specific probe. Hum Immunol 18: 65–73, 1987
Parham, P.: Making just the right match. Nature 350: 111–112, 1991
Rojo, S., Aparicio, P., Choo, S. Y., Hansen, J. A., López de Castro., J. A.: Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of aminoacid changes within a single polypeptide segment generate polymorphism in HLA-B27. J Immunol 139: 831–836, 1987a
Rojo, S., Aparicio, P., Hansen, J. A., Choo, S. Y., and López de Castro, J. A.: Structural analysis of an HLA-B27 functional variant, B27d, detected in American Blacks. J Immunol 139: 3396–3401, 1987b
Saiki, R. H., Bugawan, T. L., Horn, G. T., Mullis, K. B., and Erlich, H. A.: Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature 324: 163–166, 1986
Schlosstein, L., Terasaki, P. J., Bluestone, R., and Pearson, C. M.: High association of HLA antigen W27 with ankylosing spondilitys. N Engl J Med 288: 704–706, 1973
Seeman, G. H. A., Rein, R. S., Brown, C. S., and Ploehg, H. L.: Gene conversion generates polymorphism in human class-I genes. EMBO J 5: 547–552, 1986
Van Seventer, G. A., van der Horst, A. R., Waal, L. P., Reekers, P., and Ivanyi, P.: Antigen Society 13 Report (B7, B27, Bw47, Bw73): Public Determinants of the HLA-B7 CREG defined by Antibodies and T-Cell Clones. In Bo Dupont (ed.): Immunobiology of HLA, pp. 204–206, Springer, New York, 1989
Vega, M. A., Wallace, L., Rojo, S., Aparicio, P., and López de Castro, J. A.: Delineation of functional sites in HLA-B27 antigens. Molecular analysis of HLA-B27 variant WewaK I defined by cytolytic T lymphocytes. J Immunol 135: 3323–3332, 1985a
Vega, M. A., Ezquerra, A., Rojo, S., Aparicio, P., Bragado, R., and López de Castro, J. A.: Structural analysis of an HLA-B27 functional variant: identification of residues that contribute to the specificity of recognition by cytolytic T lymphocytes. Proc Natl Acad Sci USA 82: 7394–7398, 1985b
Vega, M. A., Bragado, R., Ivanyi, P., Pelaez, J. L., and López de Castro, J. A.: Molecular analysis of a functional subtype of HLA-B27. A possible evolutionary pathway for HLA-B27 polymorphism. J Immunol 137: 3557–3565, 1986
Weiss, E. H., Kuon, W., Dorner, C., Lang, M., and Riethmuller, G.: Organization, sequence and expression of the HLA-B27 gene. A molecular approach to analyze HLA and disease associations. Immunobiology 170: 376–380, 1985
Woodrow, J. C.: Histocompatibility antigens and rheumatic diseases. Sem Arth Rheum 6: 257–276, 1977
Yang, S. Y.: Population analysis of class I HLA antigens by one-dimensional isoelectric focusing gel electrophoresis: workshop summary report. In Bo Dupont (ed.): Immunobiology of HLA, pp. 309–331, Springer, New York, 1989
Zemmour, J. and Parham, P.: HLA class I nucleotide sequences. Tissue Antigens 37: 174–180, 1991
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Dominguez, O., Coto, E., Martinez-Naves, E. et al. Molecular typing of HLA-B27 alleles. Immunogenetics 36, 277–282 (1992). https://doi.org/10.1007/BF00215655
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DOI: https://doi.org/10.1007/BF00215655